STAT3 and ATF-2 are related to phosphatidic acid-induced Bcl-2 expression In HeLa cells

초록

Phosphatidic acid (PA), the product of PLD-mediated reaction, is lipid second messenger that participates in various intracellular signaling events and regulates a growing list of signaling protein. We found that Bcl-2 was upregulated by PA treatment in HeLa cell. However, how PA upregulates Bcl-2 expression have not been studied yet. In this study, we tried to find out the mechanism of Bcl-2 up-regulation by PA treatment in HeLa cells. Treatment with PA resulted in significantly increased expression of Bcl-2 in HeLa cells. Moreover PA-induced Bcl-2 expression was blocked by mepacrine, an inhibitor of phospholipase A2 (PLA2), whereas had no effect by propranolol, an inhibitor of PA phospholydrolase (PAP). Treatment of 1,2-Dipalmitoryl-sn-Glycero-3-phosphate (DPPA) also increased Bcl-2 expression. These results indicating that Bcl-2 expression is mediated by lysophosphatidic acid (LPA), not by arachidonic acid. PA has been reported that diversity of signaling molecules such as protein tyrosine kinase, ERK1/2phosphorylation and phosphatidylinositol 3 kinase. To investigate the relation between ERK1/2 MAPK and PA-induced Bcl-2 expression, we used MEK1/2 inhibitor, PD98059. PA-induced Bcl-2 expression was decreased when ERK1/2 is inhibited by PD98059. From these results, we tried to find out transcription factor controlled by ERK1/2 MAPK using siRNA transfection. STAT3 siRNA and ATF-2 siRNA treatments inhibited PA-induced Bcl-2 expression, respectively, suggesting that STAT3 (ser727) and ATF-2 are closely related with PA-induced Bcl-2 expression. Taken together, these findings indicate that PA is important in Bcl-2 expression through by producing LPA which is involved activation of STAT3 (ser727) and ATF-2 through ERK1/2 MAPK pathway.